@article{64e6f4a7f6b14cef849f07361de4e4df,
title = "Comparison of the Respiratory Resistomes and Microbiota in Children Receiving Short versus Standard Course Treatment for Community-Acquired Pneumonia",
abstract = "Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P , 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible.",
keywords = "antibiotic resistance, children, community-acquired pneumonia, microbiota, resistome, respiratory tract infections",
author = "Pettigrew, {M. M.} and J. Kwon and Gent, {J. F.} and Y. Kong and M. Wade and Williams, {D. J.} and Creech, {C. B.} and S. Evans and Q. Pan and Walter, {E. B.} and Martin, {J. M.} and Gerber, {J. S.} and Newland, {J. G.} and Hofto, {M. E.} and Staat, {M. A.} and Fowler, {V. G.} and Chambers, {H. F.} and Huskins, {W. C.}",
note = "Funding Information: We declare the following competing interests. V.G.F. reports personal consultancy fees from Novartis, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Basilea, Affinergy, Janssen, xBiotech, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, and Aridis; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio; a patent pending in sepsis diagnostics; educational fees from Green Cross, Cubist, Cerexa, Durata, Theravance, and Debiopharm; and an editor{\textquoteright}s stipend from IDSA. C.B.C. reports personal consultancy fees from Astellas, Vir Biotechnology, Horizon Therapeutics, Altimmune, and Premier Healthcare; grants from Merck and GSK; and royalties from UpToDate. J.M.M. reports grants from NIH and Merck and consultancy fees from Merck. W.C.H. is a member of the Endpoint Adjudication Committee for Pfizer and an advisory board member for ADMA Biologics. E.B.W. reports potential conflicts due to research support received from Pfizer and Moderna and as a member of a scientific advisory board for Vaxcyte. Funding Information: Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number UM1AI104681. Funding Information: Editor Martin J. Blaser, Rutgers University Copyright {\textcopyright} 2022 Pettigrew et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Address correspondence to M. M. Pettigrew, melinda.pettigrew@yale.edu. The authors declare a conflict of interest. VGF reports personal consultancy fees from Novartis, Novadigm, Durata, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., Cerexa, Tetraphase, Trius, MedImmune, Bayer, Theravance, Basilea, Affinergy, Janssen, xBiotech, Contrafect, Regeneron, Basilea, Destiny, Amphliphi Biosciences. Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis; Grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius; Genentech, Regeneron, Basilea, Janssen, Royalties from UpToDate; Stock options Valanbio; a patent pending in sepsis diagnostics; educational fees from Green Cross, Cubist, Cerexa, Durata, Theravance, and Debiopharm; and an editor's stipend from IDSA. CBC reports personal consultancy fees from Astellas, Vir Biotechnology, Horizon Therapeutics, Altimmune, Premier Healthcare; grants from Merck and GSK; royalties from UpToDate. JMM reports grants from NIH and Merck and consultancy fees from Merck. WCH is a member of Endpoint Adjudication Committee for Pfizer and advisory board member for ADMA Biologics. E.B.W reports potential conflicts due to research support received from Pfizer and Moderna and as a member of a scientific advisory board for Vaxcyte. Received 25 January 2022 Accepted 28 February 2022 Published 24 March 2022 Publisher Copyright: {\textcopyright} 2022 Pettigrew et al.",
year = "2022",
month = apr,
doi = "10.1128/mbio.00195-22",
language = "English",
volume = "13",
journal = "mBio",
issn = "2161-2129",
number = "2",
}